公开(公告)号：US20050020523A1

公开(公告)日：2005-01-27

申请号：US10732218

申请日：2003-12-11

申请人： Eugen Uhlmann ,  Anuschirwan Peyman ,  David Will ,  Esther Chang ,  Kathleen Pirollo ,  Antonina Rait

发明人： Eugen Uhlmann ,  Anuschirwan Peyman ,  David Will ,  Esther Chang ,  Kathleen Pirollo ,  Antonina Rait

IPC分类号： C12N15/113 ,  A61K31/133 ,  A61K31/175 ,  A61K31/407 ,  A61K31/513 ,  A61K31/519 ,  A61K31/664 ,  A61K31/675 ,  A61K31/70 ,  A61K31/704 ,  A61K31/711 ,  A61K33/24 ,  A61K38/00 ,  A61K45/06 ,  A61K48/00 ,  A61P35/00 ,  C07H21/00 ,  C07H21/02 ,  C12N15/09

CPC分类号： C07H21/02 ,  A61K38/00 ,  C12N15/1135 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/322 ,  C12N2310/345 ,  C12N2310/351 ,  C12N2310/3531

摘要： The invention relates to a specific modified oligonucleotide complementary to a section of the human Ha-ras gene and mRNA, and its use to specifically regulate, modulate or inhibit expression of the HA-ras gene, and its use as a pharmaceutical for the treatment of conditions arising from the abnormal expression of the Ha-Ras gene, in particular in combination with chemotherapy and radiotherapy. The modified oligodeoxynucleotide according to the invention has the sequence 5′-TxAxTxTxCxCxGxTxCxAxT-3′-O—PO2—O—R (SEQ ID NO:1), wherein X is an internucleotide linkage of type o or s, with the proviso that x is an s linkage at least 4 times and at most 9 times, and o means a phosphodiester internucleoside linkage, s means a phosphorothioate internucleoside linkage, R means a C8-C21 alkyl group, —(CH2—CH2O)n-(CH2)m—CH3, or —CH2—CH(OH)CH2O—(CH2)q—CH3 wherein n is an integer from 1 to 6, m is an integer from 0 to 20 and q is an integer from 7 to 20 and A is 2′-deoxyadenosine, G is 2′-deoxyguanosine, C is 2′-deoxycytidine and T is thymidine.

摘要翻译： 本发明涉及与人Ha-ras基因和mRNA的部分互补的特异性修饰寡核苷酸及其用于特异性调节，调节或抑制HA-ras基因表达的用途及其作为治疗用途的药物的用途 Ha-Ras基因异常表达引起的病情，特别是与化疗和放疗相结合。 根据本发明的修饰的寡脱氧核苷酸具有序列5'-TxAxTxTxCxCxGxTxCxAxT-3'-O-PO2-OR（SEQ ID NO：1），其中X是o或s型的核苷酸间键，条件是x是 s是至少4次，最多9次，o表示磷酸二酯核苷间键，s表示硫代磷酸酯核苷间键，R表示C8-C21烷基， - （CH2-CH2O）n-（CH2）m-CH3 ，或-CH 2 -CH（OH）CH 2 O-（CH 2）q -CH 3，其中n为1至6的整数，m为0至20的整数，q为7至20的整数，A为2'- 脱氧腺苷，G为2'-脱氧鸟苷，C为2'-脱氧胞苷，T为胸苷。

公开(公告)号：US06723706B2

公开(公告)日：2004-04-20

申请号：US09423198

申请日：2000-02-17

申请人： Eugen Uhlmann ,  Anuschirwan Peyman ,  David William Will ,  Esther Chang ,  Kathleen Pirollo ,  Antonina Rait

发明人： Eugen Uhlmann ,  Anuschirwan Peyman ,  David William Will ,  Esther Chang ,  Kathleen Pirollo ,  Antonina Rait

IPC分类号： A61K4800

CPC分类号： C07H21/02 ,  A61K38/00 ,  C12N15/1135 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/322 ,  C12N2310/345 ,  C12N2310/351 ,  C12N2310/3531

摘要： The invention relates to a specific modified oligonucleotide complementary to a section of the human Ha-ras gene and mRNA, and its use to specifically regulate, modulate or inhibit expression of the HA-ras gene, and its use as a pharmaceutical for the treatment of conditions arising from the abnormal expression of the Ha-Ras gene, in particular in combination with chemotherapy and radiotherapy. The modified oligodeoxynucleotide according to the invention has the sequence 5′-TxAxTxTxCxCxGxTxCxAxT-3′-O—PO2—O—R (SEQ ID NO:1), wherein X is an internucleotide linkage of type o or s, with the proviso that x is an s linkage at least 4 times and at most 9 times, and o means a phosphodiester internucleoside linkage, s means a phosphorothioate internucleoside linkage, R means a C8-C21 alkyl group, —(CH2—CH2O)n-(CH2)m—CH3, or —CH2—CH(OH)CH2O—(CH2)q—CH3 wherein n is an integer from 1 to 6, m is an integer from 0 to 20 and q is an integer from 7 to 20 and A is 2′-deoxyadenosine, G is 2′-deoxyguanosine, C is 2′-deoxycytidine and T is thymidine.

摘要翻译： 本发明涉及与人Ha-ras基因和mRNA的部分互补的特异性修饰寡核苷酸及其用于特异性调节，调节或抑制HA-ras基因表达的用途及其作为治疗用途的药物的用途 Ha-Ras基因异常表达引起的病情，特别是与化疗和放疗相结合。 根据本发明的修饰的寡脱氧核苷酸具有序列5'-TxAxTxTxCxCxGxTxCxAxT-3'-O-PO2-OR（SEQ ID NO：1），其中X是o或s型的核苷酸间键，条件是x是 s是至少4次，最多9次，o表示磷酸二酯核苷间键，s表示硫代磷酸酯核苷间键，R表示C8-C21烷基， - （CH2-CH2O）n-（CH2）m-CH3 ，或-CH 2 -CH（OH）CH 2 O-（CH 2）q -CH 3，其中n为1至6的整数，m为0至20的整数，q为7至20的整数，A为2'- 脱氧腺苷，G为2'-脱氧鸟苷，C为2'-脱氧胞苷，T为胸苷。